This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The folding mechanism of ?F508 CFTR is investigated under different confinement conditions. Nanosized confined system that include the mutant/wt protein are designed to mimic the cellular environment. Confining the solvent is another importatn factor that is accounted for in our models. This requires simulating large systems using explicit solvent model. These simulations will help improve our understanding of the misfolding of CFTR in living systems.